Bahler D W, Levy R
Department of Medicine, Stanford University Medical Center, CA 94305.
Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6770-4. doi: 10.1073/pnas.89.15.6770.
The potential role antigens play in growth stimulation or in clonal selection of follicular lymphomas is unknown. To study this issue, we sequenced the immunoglobulin heavy chain variable region genes expressed by a follicular lymphoma from multiple biopsy specimens and also cloned and sequenced the corresponding germ-line variable gene from this patient. Comparison to the germ-line gene revealed numerous nucleotide substitutions in all of the lymphoma variable gene sequences. Some of the substitutions may have occurred in the nonmalignant precursor B cell that gave rise to this lymphoma because they were shared among all of the variable genes, but many of the mutations accumulated as the malignant clone expanded. The mutations were distributed in such a way that strongly suggested the majority of tumor cells had been positively selected through their antigen receptor. This was especially evident for the mutations that developed late in the clonal evolution of this lymphoma. These findings indicate that antigen stimulation may be involved in the growth of follicular lymphoma tumors.
抗原在滤泡性淋巴瘤的生长刺激或克隆选择中所起的潜在作用尚不清楚。为了研究这个问题，我们对来自多个活检标本的滤泡性淋巴瘤所表达的免疫球蛋白重链可变区基因进行了测序，并从该患者身上克隆并测序了相应的种系可变基因。与种系基因相比，所有淋巴瘤可变基因序列中均发现了大量核苷酸替换。其中一些替换可能发生在产生该淋巴瘤的非恶性前体B细胞中，因为它们在所有可变基因中都有，但是许多突变是随着恶性克隆的扩增而积累的。突变的分布强烈表明，大多数肿瘤细胞是通过其抗原受体进行阳性选择的。这在该淋巴瘤克隆进化后期出现的突变中尤为明显。这些发现表明，抗原刺激可能参与了滤泡性淋巴瘤肿瘤的生长。
